Effects of Varenicline as an Adjunct to Analgesic and Anti-Inflammatory Therapy in Acute Nerve Injury

Abstract

Introduction: Acute nerve injury (ANI) leads to significant neuropathic pain and functional impairment. Current treatments, including nonsteroidal anti-inflammatory drugs (NSAIDs) like meloxicam, provide symptomatic relief but have limited neuroregenerative effects. Varenicline, a nicotinic acetylcholine receptor (nAChR) agonist, has demonstrated neuroprotective and anti-inflammatory properties. Aim: This study evaluates the effects of varenicline as an add-on therapy to meloxicam in a rat model of ANI. Methods: Eighteen female Wistar rats were randomized into four groups: Control (CONT), Sham (SHAM), Acute Nerve Injury + Meloxicam (ANI+Melox), and Acute Nerve Injury + Meloxicam + Varenicline (ANI+Melox+VAR). Varenicline (2.5 mg/kg, s.c.) was administered alongside meloxicam (2 mg/kg, s.c.). Functional recovery, histopathological changes, and biochemical markers, including prostaglandins (PGE2, PGI2), substance P, IL-6, levels, were assessed after 30 days. Results: Varenicline and meloxicam co-treatment significantly reduced inflammatory and pain biomarkers including prostaglandins, interleukin-6 and substance P, compared to meloxicam alone. Histopathological evaluation revealed enhanced Schwann cell proliferation, reduced fibrosis, and increased Bands of B & uuml;ngner formation, suggesting nerve regeneration. Conclusion: Varenicline, as an adjunct to meloxicam, enhances neuroprotection, reduces inflammation, and promotes histological and biochemical indicators of regeneration in rats with acute sciatic nerve injury. Future studies should explore its long-term effects and potential as a monotherapy for peripheral nerve injuries.